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Georgetown Lombardi researcher awarded 'Provocative Question' grant from NCI
Date:9/5/2012

derful head twice in a series of discoveries that led up to Byers successful bid to answer his "PQ."

"Twofer" the price of one

Byers, also associate director for Georgetown Lombardi's Shared Resources and director of the Translational Technologies and Resources component of the Georgetown/Howard Universities Clinical and Translational Science Center, has long studied cadherin-11, an adhesion molecule that basically sticks cells together. The gene, and its protein, regulates the way that cancer cells can invade other tissues.

The Byers group and other laboratories have found that cadherin-11 is over-expressed in some aggressive breast cancers, and in the brain tumor glioblastoma. "What these cancers have in common is cadherin-11, and a poor prognosis, with no effective therapies," he says.

Up north, Harvard University's Michael Brenner, M.D., a member of the National Academy of Sciences and the Theodore Bayles Professor of Medicine, was simultaneously working on rheumatoid arthritis, and he found that cadherin-11 is one of the major targets of this immune disease. In other words, animals in which the molecule is "knocked out" do not develop rheumatoid arthritis. Brenner and his colleagues then produced antibodies to cadherin-11 to test treatment of the disorder.

That suggested that cadherin-11 antibodies designed to treat rheumatoid arthritis might also work against cancer, says Byers who was in close contact with Brenner. Shahin Assefnia in the Byers group is now testing the Brenner antibody in animal models of tumors that over-express the molecule.

At the same time, Byers and his team, which included Georgetown Lombardi drug designers Milton Brown, Ph.D., and Sivanesan Dakshanamurthy, Ph.D., had simultaneously made a small molecule, dubbed sd133, to block cadherin-11.

Three drugs that may all do the same wonderful thing

Not long after, on one sunny serendipitous day, Dakshanamurthy walked into Byers lab. Dakshanamur
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Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

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